Lithium augmentation in treatment-resistant depression: influence of polymorphisms in tryptophan hydroxylase 2 gene (TPH2) on therapy response

In the therapy of treatment-resistant depression lithium augmentation has been shown to be an effective method. About 50% of lithium-augmented patients respond to this strategy (Bauer et al., 2003). Nevertheless, mechanisms and predictors for the clinical efficacy of lithium augmentation are still unknown, although genetic factors (for example by modulating serotonergic neurotransmission) are discussed to play an important role for the treatment response (Serretti et al., 2002; Serretti et al., 1999). Results of our own study group suggest an influence of a polymorphism in the 5HTTLPR (Stamm et al., submitted). This study investigates the association between genetic polymorphisms of tryptophane-hydroxylase type 2 (TPH2) and the response to lithium augmentation treatment in 49 patients with treatment-resistant depression. The Cox-Regression-Survival-Analysis showed no significant difference between the three TPH2 genotypes. Further results including a bigger sample are pending and expected for summer 2005. We also await results on the possible association with other genetic polymorphisms (for example G-protein beta–3). Furthermore, possible interactions of these genetic polymorphisms and their common effect on treatment response to lithium augmentation shall be investigated.